Binge eating disorder (BED), the most prevalent formal eating disorder, is associated strongly with obesity and bio-psychosocial impairment. Improved treatments for obese patients with BED are needed that can produce sustained clinical outcomes and promote weight loss. This renewal application builds on previous project. This study aims to perform a two-stage RCT to test the effectiveness of behavioral weight loss (BWL) and pharmacological treatment with Naltrexone/Bupropion (NB; a recently FDA-approved anti-obesity combination medication), alone and in combination, for the treatment of BED in obese patients. The first stage RCT will provide new findings regarding the effectiveness of NB medication and whether this specific combination of BWL and NB medication is effective for obese patients with BED. The second stage RCT will provide novel findings from a controlled test, amongst Responders to Stage 1, whether NB medication results in superior maintenance and lower-term outcomes than placebo. The second stage RCT will also explore using a controlled test, amongst Non-responders to Stage 1 treatment, whether adding cognitive-behavioral therapy (CBT) enhances on-going pharmacotherapy (NB/placebo). In Stage 1 RCT, N=160 obese patients with BED will be randomly assigned (double-blind) in a balanced factorial (2 X 2) design trial, to one of four 16-week interventions: BWL+NB, BWL+Placebo, NB, or Placebo. In Stage 2 RCT, ?Responders? to Stage 1 treatments (defined as 65% or greater reduction in binge eating) will be randomized in equal proportions (stratified blocked randomization with Stage 1 treatment as stratifying variable) to NB or placebo (double-blind) for 16 weeks. ?Non-responders? to Stage 1 treatments will continue on-going pharmacotherapy (NB/placebo; double-blind) with 50% randomized to also receive CBT. Independent evaluators will perform comprehensive assessments of both binge eating and obesity and their associated outcomes through 12-month follow-ups (i.e., 20 months after initial randomization). This study will produce important new information about the relative efficacy of BWL and this recently FDA-approved anti-obesity NB medicine), alone and in combination, for BED in obese patients. This study will produce new and novel information regarding whether amongst Responders to initial acute treatments, NB medication results in superior maintenance and longer term outcomes than placebo. This study will produce important findings regarding predictors, moderators, and mediators of outcomes that have implication for empirically-guided prescription and further refinement of treatments. Finally, this study will produce novel information regarding whether amongst Non-responders to initial acute treatments, adding CBT enhances on- going pharmacotherapy outcomes.